Search Results (69)

Introduction: Skeletal muscle (SkM) abnormalities are well-recognised in heart failure (HF). We aimed to systematically review studies of SkM energetics in patients with HF at rest and post-exercise using ³¹phosphorus magnetic resonance spectroscopy (³¹P MRS). Methods: A systematic search of cross-sectional studies used predefined search terms related to HF, SkM energetics, and ³¹P MRS (PROSPERO ID: CRD42023434698). Inclusion criteria for studies are as follows: 1. HF participants versus controls; and 2. SkM energetics assessed using ³¹P MRS reporting BOTH (i) PCr recovery time and (ii) PCr ratios (PCr/Pi and/or PCr/ATP). The primary outcome was SkM PCr recovery time following exercise, comparing patients with diagnosed HF and healthy controls and reported as standardised mean difference (SMD). Results: Of 465 identified studies, 6 met the inclusion criteria and were conducted from 1987 to 2021, comprising 162 participants (N = 86 HF, N = 76 healthy controls). HF patients (mean age 55.1 ± 4.16 years, 49 (56.9%) male) were reasonably matched to healthy controls (mean age 50 ± 8.9 years, 54 (71%) males). Two studies did not report patients’ ejection fractions (EF); the mean EF among patients from the remaining six studies was 24.8%. No studies specifically included participants with HFpEF and none characterised sarcopenia. HF patients exhibited impaired SkM energetics compared to healthy controls, which were characterised by a significantly increased PCr recovery time (SMD: −1.35, CI: −2.11, −0.59). Conclusions: PCr recovery is significantly impaired in patients with HFrEF. Females were under-represented, no HFpEF studies were identified, and no studies linking abnormal SkM energetics directly to sarcopenia were identified. Full article

Background/Objectives: Methodologies for assessing behavior form the foundation of health promotion and disease prevention. Physical activity (PA) and sedentary behavior (SB) assessment methodologies have predominantly been developed for adults without an intellectual disability (ID), raising credibility concerns for adults with ID. The purpose was to synthesize the current state of assessment methodologies for quantifying PA and SB volume in the free-living setting for adults with an ID. Methods: Following PRISMA guidelines, eleven databases were searched through December 2023, yielding 8174 records. Data were extracted in Covidence (v.2.0), obtaining quantified PA and SB volume and assessment methodology characteristics across data collection and analysis, including tool(s) and technique(s) used, preparatory actions taken, instructions provided, and behavioral strategies employed during data collection. Results: Of the 8174 articles screened, 91 met the inclusion criteria. Common metrics included minutes/hours per day/week and steps per day/week. Despite 80% of the studies using objective techniques, substantial variation existed across studies regarding wearable models, sampling frequency and epoch length settings, calibration protocols, wearable placements, and data processing techniques. Limited studies provided instructions that did not exclusively rely on spoken language. Behavioral strategies varied, including self-monitoring, providing assistance or supervision, administering questionnaires verbally, issuing reminders, and offering monetary incentives. Conclusions: This review underscores the need for greater consistency and accessibility in PA and SB assessment methodology for adults with ID. Tailored preparation, instruction, and behavioral strategies may enhance assessment viability and suitability for adults with ID, with or without caregiver or researcher involvement in the free-living setting. Full article

Background: Developmental and epileptic encephalopathies (DEE) are a group of disorders often linked to de novo mutations, including those in the ATP6V1A gene. These mutations, particularly dominant gain-of-function (GOF) variants, have been associated with a spectrum of phenotypes, ranging from severe DEE and infantile spasms to milder conditions like autism spectrum disorder and language delays. Methods: We aim to expand ATP6V1A-related disease spectrum by describing a six-year-old boy who presented with a febrile seizure, mild intellectual disability (ID), language delay, acquired microcephaly, and dysmorphic features. Results: Genetic analysis revealed a novel de novo heterozygous pathogenic variant (c.82G>A, p.Val28Met) in the ATP6V1A gene. He did not develop epilepsy, and neuroimaging remained normal over five years of follow-up. Although ATP6V1A mutations have traditionally been linked to severe neurodevelopmental disorders, often with early-onset epilepsy, they may exhibit milder, non-progressive phenotypes, challenging previous assumptions about the severity of ATP6V1A-related conditions. Conclusions: This case expands the known clinical spectrum, illustrating that not all patients with ATP6V1A mutations exhibit severe neurological impairment or epilepsy and underscoring the importance of including this gene in differential diagnoses for developmental delays, especially when febrile seizures or dysmorphic features are present. Broader genotype–phenotype correlations are essential for improving predictive accuracy and guiding clinical management, especially as more cases with mild presentations are identified. Full article

N-glycan, a critical quality attribute (CQA) of monoclonal antibodies, profoundly impacts potency, immunogenicity, safety, and clinical efficiency. Therefore, N-glycan should be monitored and controlled during development. The conventional 2-AB method is considered the gold standard for N-glycan analysis, which is labor intensive and time consuming. Moreover, its sample requirement is relatively high and cannot be met in early-stage development, including cell line development. In this study, we compared the performance of four rapid analytical methods in N-glycan analysis of mAbs, including the rapid 2-AB method, reduction method, off-line IdeS digestion method, and two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS) method. Our results showed that these four rapid analytical methods could provide comparable N-glycan data. Moreover, these four rapid methods shortened the testing time for the conventional 2-AB method from days to just minutes. They also reduced the sample requirement for the conventional 2-AB method from milligrams to micrograms. Among these four rapid methods, the 2D-LC-MS method demonstrated great potential for applications in time-consuming cell line development because it required less testing time and a lower sample requirement. Full article

11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor bioavailability of 11β-MNT. To elucidate the role of the first-pass metabolism of 11β-MNT in its poor bioavailability, we determined the biotransformation products of 11β-MNT and its prodrugs in human in vitro models. 11β-MNT and its two prodrugs 11β-MNTDC and 11β-MNT undecanoate (11β-MNTU) were incubated in cryopreserved human hepatocytes (HHs) and subjected to liquid chromatography–high resolution tandem mass spectrometry analysis, which identified ten 11β-MNT biotransformation products with dehydrogenated and glucuronidation (11β-MNTG) metabolites being the major metabolites. However, 11β-MNTG formation is highly variable and prevalent in human intestinal S9 fractions. A reaction phenotyping study of 11β-MNT using thirteen recombinant UDP-glucuronosyltransferase (UGT) enzymes confirmed the major role of UGT2B17 in 11β-MNTG formation. This was further supported by a strong correlation (R² > 0.78) between 11β-MNTG and UGT2B17 abundance in human intestinal microsomes, human liver microsomes, and HH systems. These results suggest that 11β-MNT and its prodrugs are rapidly metabolized to 11β-MNTG by the highly polymorphic intestinal UGT2B17, which may explain the poor and variable bioavailability of the drug. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management. Full article

The scientific literature was reviewed with the aim of analysing the state of the art on the role of nursing in the management of chemotherapy extravasation, recognising the possible risk factors and identifying effective training programmes for nurses. WOS, Scopus, and PubMed databases were used to perform the searches. Papers that met the inclusion criteria and that had been published in the last 9 years were selected. The Effective Public Health Practice Project (EPHPP) instrument was applied to the selected studies. In addition, this research was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: 512480). Out of the 23 initially selected articles, a total of 9 articles were eventually included, since they met the eligibility criteria that were established after a more exhaustive analysis, which included reading their abstracts and full texts. The results show that the management of chemotherapy extravasation is closely related to factors that largely depend on the nursing staff. Among the most relevant findings are factors including the identification of the nursing role in the management of extravasation due to chemotherapy; risk factors; and effective training programmes for nursing. Nurses play a crucial role throughout the entire process of treatment, prevention, and health education in chemotherapy treatment. Training programmes for nurses are fundamental, as they increase their professional competence and improve the safety of the patient. Adequate knowledge of chemotherapy treatment and the risk factors of extravasation are basic elements for the prevention of this type of injury, as well as for the improvement of the quality of life of patients under this kind of intravenous therapy. Full article

Immediate dentin sealing (IDS) is a method of improving the bond strength of indirect dental restorative materials to dentin and belongs to the biomimetic protocols of contemporary dentistry. The purpose of this systematic review was to evaluate the effect of IDS on the bond strength of resin-based CAD/CAM materials to dentin. PubMed and MEDLINE, Scopus, and the Web of Science were searched by two individual researchers, namely for studies that have been published in English between 1 January 2005 and 31 December 2023 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The inclusion criteria encompassed articles related to in vitro studies, measuring the bond strength through microtensile bond strength (μ-TBS), micro-shear bond strength (μ-SBS), tensile bond strength (TBS) or shear bond strength (SBS) tests after the use of the IDS technique. The included restorative materials comprised resin-based CAD/CAM materials bonded to dentin. A total of 1821 studies were identified, of which 7 met the inclusion criteria. A meta-analysis was not deemed appropriate due to the high level of diversity inthe publications and techniques. The use of IDS yielded higher bond strength outcomesin various experimental conditions and resin-based CAD/CAM materials. Overall, IDS in CAD/CAM restorations may contribute to better clinical outcomesand improved restoration longevity due to this property. Full article

This systematic review aims to analyze the effects of acute and chronic exercise on appetite and appetite regulation in patients with abnormal glycemic control. PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for eligible studies. The included studies had to report assessments of appetite (primary outcome). Levels of appetite-regulating hormones were analyzed as secondary outcomes (considered, if additionally reported). Seven studies with a total number of 211 patients with prediabetes or type 2 diabetes mellitus (T2DM) met the inclusion criteria. Ratings of hunger, satiety, fullness, prospective food consumption, nausea, and desire to eat, as well as levels of (des-)acylated ghrelin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, pancreatic polypeptide, peptide tyrosine tyrosine, leptin, and spexin were considered. Following acute exercise, the effects on appetite (measured up to one day post-exercise) varied, while there were either no changes or a decrease in appetite ratings following chronic exercise, both compared to control conditions (without exercise). These results were accompanied by inconsistent changes in appetite-regulating hormone levels. The overall risk of bias was low. The present results provide more evidence for an appetite-reducing rather than an appetite-increasing effect of (chronic) exercise on patients with prediabetes or T2DM. PROSPERO ID: CRD42023459322. Full article

Motivational climate is known to relate to individual behaviors, emotions, and thoughts. Hedonic or subjective well-being includes self-assessed positive affect (i.e., pleasant affect, moods, and emotions), negative affect (i.e., unpleasant affect, moods, and emotions), and life or domain-specific satisfaction. The aim of this review was to quantify the relationships between task and ego motivational climate scales and measures representing hedonic well-being with sports participants. Potential moderators of the motivational climate and hedonic well-being were examined. This review followed the PRISMA guidelines (PROSPERO ID CRD42023470462, registered 28 October 2023). From five relevant databases, one relevant review, and hand searching, 82 articles totaling 26,378 participants (46.3% female) met the inclusion criteria. The articles spanned publication dates from 1993 to 2023, representing 18 countries, various team and individual sports, and athletes competing in elite (e.g., Olympic) to grassroot (e.g., club sport) competitions. To meta-analyze the motivational climate and hedonic well-being relationships, the random-effects model was used. For the moderation analyses, the mixed-effects model was used. The task or mastery climate relationships were medium in magnitude with positive affect and satisfaction and small with negative affect. The ego or performance climate relationships were small in magnitude for positive affect, negative affect, and satisfaction. Evidence of bias existed in the motivational climate and hedonic well-being relationships. For moderation analyses, athlete level (i.e., elite vs. non-elite) moderated (p < 0.05) the task (elite, r = 0.23; non-elite, r = 0.34) and ego motivational climate (elite, r = −0.02; non-elite, r = −0.13) and positive affect and satisfaction combined relationships. In conclusion, the motivational climate and hedonic well-being relationships were stronger for the task climate than for the ego climate. The finding that elite athlete correlations appeared dampened is important for future research. Even with the damped relationships, practitioners, from the Olympics to local clubs, should ensure the promotion of the task climate to maximize positive affect and satisfactions in and around the sport experience. Full article

Background: Intraoral adenoid cystic carcinoma (ACC) arising from minor salivary glands (MSG) is a rare malignancy associated with delayed diagnosis and unfavorable outcomes. This study aimed to comprehensively review ACC of MSGs, focusing on clinical characteristics, imaging modalities, treatment approaches, and long-term outcomes. Methods: A systematic search was conducted in PubMed, Web of Science, and MEDLINE databases to identify relevant articles reporting cases of ACC of MSGs between January 1997 and March 2023. The study was registered in PROSPERO (ID: CRD42023449478). A total of 10 studies that met the inclusion criteria were selected for critical review. In total, 902 patients were diagnosed with ACC of MSGs with an age range of 44.3 to 63 years, and an average age of 56.6 years. The female to male ratio ranges from 1:1 to 2.4:1. Regarding the primary site of ACC, the palate was the most common location, accounting for 30.5% to 83.3%, followed by the buccal mucosa, floor of the mouth, and lip and the retromolar area. For histology, the solid mass pattern was the most prevalent, seen in 95.2% of patients, followed by the cribriform pattern. Regarding treatment modalities, surgery was the most common approach, applied in 76.3% of cases, with a combination of surgery and radiotherapy used in 29.0% of cases. A smaller fraction, 3.2%, received a combination of surgery, chemotherapy, and radiotherapy, and 8.3% underwent radiotherapy alone. Local recurrence rates varied between 1% and 28.5%, and distant metastasis occurred in 18.2% to 33.3% of cases, predominantly to lymph nodes (14.5%). An analysis of overall survival across various stages and patient numbers indicated a 5-year survival rate of 68.0%. The findings of this study provide valuable insights for physicians in making treatment decisions and emphasize the need for ongoing research and collaborative clinical efforts to improve the management and outcomes of this challenging disease. Conclusion: ACC of MSGs is a multifaceted condition typically manifesting as asymptomatic enlargement and ulceration. This disease is marked by distinct histopathological patterns and perineural invasion (PNI). Recognizing these distinctive aspects is key in shaping the treatment plan, which can range from surgical procedures to radiation therapy, chemotherapy, and evolving targeted treatments. Continuous research and collaborative clinical efforts remain critical for ongoing progress in the treatment and management of this challenging condition. Full article

This study focuses on improving pre-emptive risk recognition and safety checks to prevent workplace accidents. It underscores improvements by addressing existing research issues, suggesting potential enhancements through system development. Work approval procedures and workers’ prior risk awareness, through the confirmation of work safety standards in physically separated work areas, are fundamental methods of preventing serious accidents and creating a safe work environment. A key factor concerning worker safety is recognizing the potential accident risk factors (or hazards) in advance through practical job hazard analysis and consequently take risk-reduction measures in case the safety standards are not met. Despite the crucial significance of pre-awareness of work risks at the majority of construction sites, tools to enhance this awareness are currently limited. Furthermore, real-time detection of work risks and the implementation of risk reduction measures are contingent upon a monitoring environment and a robust safety culture. This study proposed construction worker location-tracking technology that recognizes personal identification (ID). A safety check system based on location tracking combining personal quick response code (QR code) recognition and computer vision technology to automatically identify workers’ personal identities and track their physical location was proposed. A real-time safety check system was implemented to classify automatically whether workers have confirmed hazards and to approve a work process in high-risk workplaces by supervisors. Location-tracking technology with ID recognition performed the following two safety management functions. First, if a construction worker does not pre-check the work risk information before entering the work zone, the geofencing technology automatically classifies workers as those who are not aware of job hazards. Secondly, the safety manager or supervisor entering the on-site work zone possesses the authority to halt work if the work environment fails to meet safety standards and can issue warnings regarding risky situations. Essential functions were validated through a case study involving preliminary testing within the development system. To assess the practical application of the system, virtual simulations were conducted using recorded videos from a construction site to replicate the two essential functions of the system. The system was constructed using an Apache server and Python code, and for testing purposes, the names of the workers were randomized. Full article

The prognosis of mixed-lineage leukemia (MLL) has remained a significant health concern, especially for infants. The minimal treatments available for this aggressive type of leukemia has been an ongoing problem. Chromosomal translocations of the KMT2A gene are known as MLL, which expresses MLL fusion proteins. A protein called menin is an important oncogenic cofactor for these MLL fusion proteins, thus providing a new avenue for treatments against this subset of acute leukemias. In this study, we report results using the structure-based drug design (SBDD) approach to discover potential novel MLL-mediated leukemia inhibitors from natural products against menin. The three-dimensional (3D) protein model was derived from Protein Databank (Protein ID: 4GQ4), and EasyModeller 4.0 and I-TASSER were used to fix missing residues during rebuilding. Out of the ten protein models generated (five from EasyModeller and I-TASSER each), one model was selected. The selected model demonstrated the most reasonable quality and had 75.5% of residues in the most favored regions, 18.3% of residues in additionally allowed regions, 3.3% of residues in generously allowed regions, and 2.9% of residues in disallowed regions. A ligand library containing 25,131 ligands from a Chinese database was virtually screened using AutoDock Vina, in addition to three known menin inhibitors. The top 10 compounds including ZINC000103526876, ZINC000095913861, ZINC000095912705, ZINC000085530497, ZINC000095912718, ZINC000070451048, ZINC000085530488, ZINC000095912706, ZINC000103580868, and ZINC000103584057 had binding energies of −11.0, −10.7, −10.6, −10.2, −10.2, −9.9, −9.9, −9.9, −9.9, and −9.9 kcal/mol, respectively. To confirm the stability of the menin–ligand complexes and the binding mechanisms, molecular dynamics simulations including molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) computations were performed. The amino acid residues that were found to be potentially crucial in ligand binding included Phe243, Met283, Cys246, Tyr281, Ala247, Ser160, Asn287, Asp185, Ser183, Tyr328, Asn249, His186, Leu182, Ile248, and Pro250. MI-2-2 and PubChem CIDs 71777742 and 36294 were shown to possess anti-menin properties; thus, this justifies a need to experimentally determine the activity of the identified compounds. The compounds identified herein were found to have good pharmacological profiles and had negligible toxicity. Additionally, these compounds were predicted as antileukemic, antineoplastic, chemopreventive, and apoptotic agents. The 10 natural compounds can be further explored as potential novel agents for the effective treatment of MLL-mediated leukemia. Full article

Our group previously demonstrated that Caesalpinia mimosoides Lamk exhibits many profound biological properties, including anticancer, antibacterial, and antioxidant activities. However, its antiviral activity has not yet been investigated. Here, the aqueous extract of C. mimosoides was prepared from the aerial parts (leaves, stalks, and trunks) to see whether it exerts anti-influenza (H1N1) effects and to reduce the organic solvents consumed during extraction, making it a desirable approach for the large-scale production for medical uses. Our plant extract was quantified to contain 7 g of gallic acid (GA) per 100 g of a dry sample, as determined using HPLC analysis. It also exerts potent antioxidant activities comparable to those of authentic GA. According to untargeted metabolomics (UPLC-ESI(-)-QTOF-MS/MS) with the aid of cheminformatics tools (MetFrag (version 2.1), SIRIUS (version 5.8.3), CSI:FingerID (version 4.8), and CANOPUS), the major metabolite was best annotated as “gallic acid”, phenolics (e.g., quinic acid, shikimic acid, and protocatechuic acid), sugar derivatives, and dicarboxylic acids were deduced from this plant species for the first time. The aqueous plant extract efficiently inhibited an influenza A (H1N1) virus infection of MDCK cells with an IC₅₀ of 5.14 µg/mL. Of equal importance, hemolytic activity was absent for this plant extract, signifying its applicability as a safe antiviral agent. Molecular docking suggested that GA interacts with conserved residues (e.g., Arg152 and Asp151) located in the catalytic inner shell of the viral neuraminidase (NA), sharing the same pocket as those of anti-neuraminidase drugs, such as laninamivir and oseltamivir. Additionally, other metabolites were also found to potentially interact with the active site and the hydrophobic 430-cavity of the viral surface protein, suggesting a possibly synergistic effect of various phytochemicals. Therefore, the C. mimosoides aqueous extract may be a good candidate for coping with increasing influenza virus resistance to existing antivirals. Full article

Background: There is growing support for considering Dance Movement Therapy (DMT) as an effective approach to improving physical and psychological symptoms in eating disorders (ED), but additional evidence is needed. The current study aims to investigate the effectiveness of a DMT intervention for inpatients with ED during an in-hospital rehabilitation program for ED in reducing emotion dysregulation and alexithymia and improving interoceptive awareness. Methods: Forty-nine consecutive inpatient young women with ED (aged between 18 and 34 years) recruited from a clinical center for the rehabilitation of obesity and ED received four group sessions of DMT intervention. All participants completed the Difficulties in Emotion Regulation Scale (DERS), the Toronto Alexithymia Scale (TAS), and the Multidimensional Assessment of Interoceptive Awareness Scale (MAIA) before (Time 0) and after the intervention (Time 1). Paired-sample t-tests were run to assess differences between Time 0 to Time 1. Results: From pre-to-post interventions, there was a significant reduction in the means of all of the subscales of DERS, suggesting an improvement in emotion regulation competencies, with the only exception for difficulties in awareness that increased (p = 0.016). We also found a significant reduction in alexithymia, as proved by significant differences in all of the subscales and the total score of TAS (p < 0.001), and significant improvements in interoceptive awareness as suggested by increased scores of the noticing (p = 0.043), emotional awareness (p < 0.001), body listening (p < 0.001), and trusting (p < 0.001) subscales of MAIA. Conclusion: Overall, our results point towards the efficacy of dance/movement in reducing symptoms of eating disorders. Our findings also suggest that dancing can be considered a useful intervention to increase emotional regulation, reduce alexithymia, and enhance interoceptive awareness. Full article